Although right ventriculare failure and renal dysfunction occur frequently in patients with respiratory failure, the pathogenesis remains unclear. The roles of blood gas derangements, and activiation of renin-angiotensin (RAS) and arginine vasopressin (AVP) systems in the renal dysfunctions and pulmonary hypertension have not been elucidated clearly. The specific aims of this project are: 1) to determine the role of the RAS in the renal dysfunction and pulmonary and systemic hypertension observed during combined acute hypoxemia and hypercapnia; 2) to elucidate the role of AVP in diminished renal hemodynamic function, and pulmonary and systemic hypertension during combined acute hypoxemia and hypercapnia: and 3) to document the effects of chronic blood gas derangements. Five protocols will be employed using unanesthetized mongrel dogs: 1) The role of the RAS during acute hypoxemia and hypercapnia will be assessed by intrarenal infusion of the angiotensin II (AII) inhibitors (Sar1,Ala8)-AII and SQ 14,225 in doses that do not result in systemic AII blockade. Systemic vascular and renal function will be measured by conventional techniques, and plasma renin activity and AII will be measured by redioimmunoassay. 2) Systemic administration of the AII inhibitors during acute hypoxemia and hypercapnia will assess the role of RAS in the systemic and pulmonary pressor responese. 3) The role of AVP in diminished renal hemodynamic function during combined acute hypoxemia and hypercapnia will be assessed by intrarenal infusion of the AVP pressor antagonist d(CH2)5Tyr(Me)AVP in doses that do not result in systemic AVP blockade. To prevent the RAS from offsetting the effecxts of AVP blockade, d(CH2)5Tyr(Me) AVP will be administered alone, and in combination with (Sar1,Ala8)-AII. 4) Systemic administration of d(CH2)5Tyr(Me)AVP during combined acute hypoxemia and hypercapnia, will assess the role of AVP in systemic and pulmonary pressor responese. 5) The effects of chronic blood derangements (2 weeks) on systemic and pulmonary hemodynamic function and renal function and RAS and AVP will be determined. The importance of this project relates to identification of mechanisms for renal dysfunction and pulmonary and systemic hypertension during respiratory failure. As a result, new impetus may be provided to minimize blood gas derangements, and new forms of therapy may be instituted.